Ion Mobility Spectrometry (xe2x80x9cIMSxe2x80x9d) is a technique that separates ions in terms of their mobility with reference to a drift/buffer gas. The analysis is based on measuring the velocity which gaseous ions obtain while drifting a defined length through the buffer gas. Prior art mobility techniques are known as xe2x80x9ctime-of-flightxe2x80x9d separation techniques if detection is based on time, or as xe2x80x9cdifferentialxe2x80x9d separation techniques if ion detection is based on position. In either case the ion mobility can be determined from the ion drift velocity, vd, and is inversely proportional to the electric field strength, E:
Vd=K0E 
where K0 is reported at 760 Torr and 273 K and is a function of the ion volume/charge ratio and can be related to ion size and shape through the measured collision cross-section.
In many instances the ion mobility chamber is designed to produce a linear constant electric field either constructed as a series of equally spaced electrodes connected through a resistor chain, or as a tube, which has been coated with a resistive material. In one case, U.S. Pat. No. 5,789,745 to Martin et al., a traveling potential well was used to transport ions of differing mobility in hopes of miniaturizing the drift cell while maintaining resolution, but no evidence of addressing resolution is shown. U.S. Pat. No. 5,189,301 to Thekkadath constructed a cup shaped electrode, creating a non-linear field to focus ions to a detector thereby increasing sensitivity by decreasing losses due to diffusion. U.S. Pat. No. 4,855,595 to Blanchard has also used nonlinear fields for the purpose of controlling ions by trapping ions in a potential well to normalize drift differences and increase selectivity. The ""595 patent achieves ion trapping by using a sequence of electric fields; two of which move ions in the direction of the collector while the other field reverses the migration for a time by moving the ions away from the collector.
U.S. Pat. No. 5,235,182 to Avida took a different approach, using slightly focusing electric fields formed by a particular electrode width to gap ratio to increase sensitivity and claiming increased resolution, but providing no substantial evidence therein. In fact, the resolution as reported by Avida was only one-third of prior art devices. The Avida drift tube owes its slightly focusing characteristics to the fringing fields seen in the areas near the electrodes and endplates. The use of only slightly focusing fields imposes fundamental limitations on the Avida instrument. Optimal realization of the advantages of the Avida instrument and method are limited to relatively high-pressure applications and those using a broad ionization source as opposed to those using pulsed ionization methods. In these cases, an only xe2x80x9cslightlyxe2x80x9d focusing field will be insufficient to avoid a diminution in sensitivity because the traversing ions will be concentrated in the center of the drift tube where the focusing effects are non-existent. A major advancement of the present invention is the discovery that much more strongly focusing fields are obtainable using electrode configurations having dimensions outside the range of those taught by Avida. In this way, the novel dimensions and configurations taught herein are much better suited for IMS applications, which utilize pulsed ionization methods.
In one instance, Gillig constructed an IMS device using a homogeneous magnetic field to increase sensitivity by reducing ion losses due to diffusion in a linear electric field, taking advantage of the fact that a homogeneous magnetic field has no effect on mobility along the drift cell axis. It is well known in the art of spectrometry that the resolution performance of an ion mobility spectrometer is to a large degree controlled by the linearity of the electric field in the drift cell. To maximize resolution at a given voltage drop and pressure the electric field is kept as linear as possible and in fact any non-linearity will decrease resolution by increasing drift times along the axis of the instrument. Therefore, for a given voltage drop, the theoretically optimum result for an increase in sensitivity when using non-linear fields is the preservation of the analogous resolution obtained using linear fields.
Coupling of an ion mobility chamber to an orthogonal time-of-flight mass spectrometer was described in the literature in both the journal article by McKnight, L. G., et al., Phys. Rev., 164, 62 (1967), and The Mobility and Diffusion of Ions in Gases, 68-72 (1973). Clemmer, et al., in U.S. Pat. No. 5,905,258, using a similar approach, teach improvements in IMS/MS which incorporate ionization techniques more suitable for biological applications. In one aspect of the present invention, a periodic focusing ion mobility spectrometer is coupled to an orthogonal time-of-flight mass spectrometer for mass analysis purposes resulting in an improved IMS/MS.
The challenges in the field of spectrometry have continued to increase with demands for more and better techniques having greater flexibility and adaptability. Therefore, there exists a need for a new system and method for separating and analyzing ions.
In a specific embodiment of the present invention there is an apparatus for separating and analyzing ions, comprising an ion source to generate ions an ion mobility chamber positioned to receive the ions from the ion source and capable of producing a periodic focusing electric field. The ion mobility chamber comprises a plurality of outer ring electrodes and a plurality of outer ring inter-electrode gaps coupled to the outer ring electrodes, a plurality of inner ring electrodes coaxial with the outer ring electrodes and equally spaced to form an inner drift tube. The ratio of the drift tube diameter to the electrode width of any individual inner ring electrode is less than four. A resistor chain is coupled to the outside of the ion mobility chamber to apply a potential to both the outer and inner ring electrodes and an endplate is coupled to the ion mobility chamber, the endplate having an ion aperture to expel the ions. Additionally, a plurality of lenses is coupled to the ion aperture and a plurality of electrostatic steering plates coupled to the lenses and a detector coupled to the lenses.
In another specific embodiment, an apparatus for separating and analyzing ions comprises an ion source to generate ions, an ion mobility chamber positioned to receive the ions from the ion source and capable of producing a periodic focusing electric field. The ion mobility chamber comprises a plurality of ring electrodes equally spaced to form a drift tube and a plurality of inter-electrode gaps adjacent to the ring electrodes wherein the ratio of the drift tube diameter to the electrode width of any individual ring electrode is less than four. A resistor chain is coupled to the outside of the ion mobility chamber to apply a potential to the ring electrodes and an endplate is coupled to the ion mobility chamber, the endplate having an ion aperture to expel ions. A plurality of lenses is coupled to the ion aperture, a plurality of electrostatic steering plates coupled to the lenses and a detector is also coupled to the lenses.
Another embodiment involves a method of separating and analyzing ions in the presence of a gas comprising the steps of generating ions from an ion source and separating ions in terms of their mobility. The separating step comprises transporting the ions in a periodic focusing electric field. The ions are thereafter detected.
A further embodiment involves a method for transporting ions in the presence of a gas by transporting ions in a periodic focusing electric field thereby increasing the transmission efficiency of the ions from a high pressure source to high vacuum.
In the preferred apparatus embodiment using multiple coaxial series of electrodes, the ratio of the distance from the inner surface of the outer ring of electrodes to the spectrometer axis to the distance from the inner surface of the inner ring of electrodes to the spectrometer axis is less than six.
Additionally, in the preferred embodiment for all apparatuses, the detector is a mass spectrometer, preferably a time-of-flight mass spectrometer and more preferably, the drift tube of the TOFMS is orthogonal to the drift tube of the ion mobility cell.
In an alternative embodiment, the apparatus allows the multiple series of electrodes to be offset from one another by a distance up to and including one electrode width. In some cases, the series of electrodes are replaced with resistively coated metal helixes. These helixes may also be offset up to and including one unit helix thickness, such thickness being equal to thickness of the wire making up the helix.
In the preferred embodiment, the ionization source is a matrix-assisted laser desorption source.
In another embodiment, the method for separating and detecting ions using a mass spectrometer for detection.
Additionally, in the preferred method embodiment, the detector is a mass spectrometer, preferably a time-of-flight mass spectrometer and more preferably, the drift tube of the TOFMS is orthogonal to the drift tube of the ion mobility cell.
In an alternative embodiment, the method employs one series of electrodes to be offset from another series by a distance up to and including one electrode width. In some cases, the series of electrodes are replaced with resistively coated metal helixes. These helixes may also be offset up to and including one unit helix thickness, such thickness being equal to thickness of the wire making up the helix.
In the preferred embodiment, the method uses matrix-assisted laser desorption ionization.
In an alternative embodiment, a method of transporting ions in the presence of gas is described outside the context of ion mobility spectrometry. The method utilizes periodic field focussing in the single electrode series and in the multiple electrode series embodiment. In either embodiment the electrodes may be substituted by metal helixes. In the multiple series embodiment, the electrodes and helixes may be offset as described above.
The present invention provides an IMS instrument having improved sensitivity over the prior art while simultaneously preserving the resolution. In so doing, the improved IMS is particularly amenable to applications where the pressure is from 1 to hundreds of Torr with an ionization source and a small sampling aperture for sampling ions after separation in the drift tube.